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Associate Program Director, Pulmonary and Critical Care Fellowship Program

News — I’ve only had one or two significant nosebleeds in my life, after childhood scuffles on the playground. But for patients with  (HHT), frequent and sometimes intense nosebleeds are a regular occurrence.

HHT, also called Osler-Weber-Rendu syndrome, is a genetic bleeding disorder that causes abnormal development of capillaries, the tiny vessels that connect our arteries and veins. The result is unstable blood vessels, usually on the skin or in the lining of the nose and gastrointestinal (GI) tract, that can spontaneously burst and cause bleeding. Similar blood vessel abnormalities called arteriovenous malformations (AVMs) can occur in internal organs such as the brain, lungs, and liver and can lead to serious complications.

About 90% of people with HHT have spontaneous nosebleeds, which can begin in infancy and can be mild to severe. For some patients, this can mean a few tiny drops of blood on their pillow in the morning. For others, it can be a sudden deluge that disrupts sleep, interrupts a commute, or interferes with a work presentation.

Since HHT is uncommon and shares symptoms with less serious conditions, it is often misdiagnosed as migraine headaches, lung disease, allergies, or even a unique birthmark. Because of this, though HHT runs in families, generational symptom trends may go unnoticed.

Getting a proper diagnosis for HHT can be lifesaving. There are many effective treatments that can significantly reduce the risk of life-limiting complications. The UT Southwestern  is one of just 22 designated HHT Centers of Excellence in the U.S., and the only one in Texas.

If you have a personal or family history of frequent nosebleeds, talk with an HHT expert. Our specialists can help you identify the cause of your symptoms, connect family members with valuable genetic testing, and recommend gold-standard treatment to reshape your family’s health future.

How is HHT diagnosed?

Genetic testing and counseling

HHT is passed down in DNA from your parents.  can help us identify whether HHT genes are present in your family. Only one abnormal gene from one parent is needed to inherit the condition, so 50% of people with a parent with HHT will have it.

First, we work to identify a genetic mutation that results in a patient’s HHT, known as a causative gene. If one parent has the mutation, there is a 50% chance each child will have it too. Once we know which gene to look for, we can spot it efficiently in other family members. HHT does not skip a generation, so if a family member does not have that genetic variant, his or her children will not have it.

Several genes have been identified, but there likely are more that have not been discovered. Because of this, about 10% of people with clear HHT symptoms will have negative test results for known gene variants. So, those patients and their family members should be clinically examined by an HHT specialist.

Conversation about personal and family history

An HHT specialist will talk with you about your symptoms, as well as symptoms that run in the family. Along with frequent nosebleeds, HHT can cause symptoms including:

• Anemia from low iron
• Dark or black stool from bleeding in the GI tract
• Stroke, even in young people
• Abnormal blood vessels in the liver
• Seizures or unexplained small strokes from bleeding in the brain
• Shortness of breath
• Telangiectasias – red spots and lines on the lips, tongue, ears, and fingertips

HHT is sensitive to hormonal changes. People with HHT who are pregnant usually see their symptoms change before, during, and after they deliver. Sometimes, women have more severe symptoms after menopause. The same can be true for men, who also go through hormonal changes as they age.

Family history discussions with our patients are always enlightening, as many discover that seemingly unconnected symptoms reported by parents, aunts and uncles, and grandparents may be associated with HHT. Often, family members visit the clinic together, and we examine the family member who has the most severe symptoms.

"Because HHT is a hereditary condition, we get to know our patients very well, as well as several members of their family. It’s an amazing experience, and we thrive in building meaningful, longitudinal relationships with patients.”

Physical exam and imaging

Telangiectasias that form in blood vessels in the internal organs are called  (AVMs), which can cause the blood vessel to weaken, rupture, and bleed. AVMs associated with HHT appear most frequently in organs such as the brain, liver, GI tract, and lungs.

Not all AVMs cause symptoms. For example, 60% of people with HHT have AVMs in their digestive tract, but only about 20% develop GI bleeding. The longer an AVM goes undetected and untreated, the higher the risk for severe complications, including life-threatening bleeding, stroke, brain damage, and death.

Imaging exams such as saline contrast echocardiogram can look for AVMs in the lungs, and  is used to examine the brain. Our research has  of AVMs in the lungs and has shown they are  with CT scan and treated by endovascular occlusion, a minimally invasive procedure using a catheter to block the artery delivering blood to the lesion.

If we locate an AVM, specialists such as , , and  will add their expertise to your care.

Patients without a known gene variant who meet three of these four criteria can be clinically diagnosed with HHT:

• Nosebleeds that happen over and over without a good reason
• A family history of symptoms of HHT
• Telangiectasias on the lips, fingertips, and inside of the mouth
• AVMs in the organs, even if asymptomatic:
  • 70%-80% of patients with HHT have AVMs in the liver
  • 80% have them in the GI tract
  • 50% have them in the lungs
  • Fewer than 10% have them in the brain

What are the treatment options for HHT?

Depending on your symptoms, the specialist may recommend one or a combination of treatments to reduce bleeding and reduce the risk of cardiovascular complications:

• Nosebleed prevention can include using moisturizing ointments and sprays and increasing humidity in the home with a humidifier.
• Monitoring HHT involves regular checkups from a primary care provider and a specialist at an HHT Center of Excellence, imaging tests such as MRI and echocardiography to check for AVMs, and blood tests to assess iron levels.

• Coblation is a new technique to treat telangiectasias in the nose. Radiofrequency energy is used to treat lesions and control severe nosebleeds, providing relief for up to two years.
• Radiation therapy can be used to treat AVMs instead of surgery, offering another option for brain AVMs and others.
• Embolization is a minimally invasive procedure to block malformed blood vessels with tiny particles or glue-like substances to prevent bleeding. Our research shows that a , a device to reduce blood flow in lung blood vessels, can effectively embolize AVMs with fewer complications than traditional methods.
• Surgery is a good option for removing some larger or dangerous AVMs before they cause problems.

Advanced infusion therapy

Because we are an HHT Center of Excellence, our patients can access “inhibitors of angiogenesis” such as bevacizumab, a monoclonal antibody infusion treatment that uses lab-made proteins to stop abnormal blood vessels from forming.

This treatment has completely changed HHT. Dozens of our patients have described bevacizumab as a “miracle” that significantly reduces bleeding and restores energy that had been lost to chronic anemia. While the drug is not truly a miracle – it is still relatively expensive and can cause side effects such as protein in the urine and high blood pressure – it can greatly improve patients’ quality of life.

UT Southwestern researchers are working to develop oral medications that could have an effect similar to bevacizumab. If successful, a once-daily pill could be easier and more cost-effective for patients than biweekly or monthly infusions in the hospital.

Shedding light on a not-so-rare bleeding condition

Though HHT is considered a rare disease, it is more common than people might think. About 1 in 5,000 people have HHT.  also affects 1 in 5,000 people and  occurs in 1 in 2,500.

Our goal, through research and specialized care, is to empower more patients and providers with knowledge about HHT, its symptoms, and treatment options.

UT Southwestern is participating in several research studies to help us learn more about HHT and improve care. We are part of a  of the effectiveness of a daily medication to reduce nosebleed severity, and we contribute anonymized data to a  to collect data and further improve HHT awareness, diagnosis, and care.

If you or your family have frequent or severe nosebleeds, ask your doctor for a referral to an HHT expert. With proper treatment, you can take control over this disruptive bleeding disorder.

Collaborating for patients and families

UTSW has received a $300,000 grant from , a national research and advocacy organization, and funded by the U.S. Health Resources and Services Administration to build our program and empower more patients and providers with information about HHT. .